Brand Names: U.S.

Aggrastat

Pharmacologic Category

Antiplatelet Agent, Glycoprotein IIb/IIIa Inhibitor

Pharmacology

A reversible antagonist of fibrinogen binding to the glycoprotein (GP) IIb/IIIa receptor, the major platelet surface receptor involved in platelet aggregation. When administered intravenously, it inhibits ex vivo platelet aggregation in a dose- and concentration-dependent manner. When given according to the recommended regimen, >90% inhibition is attained within 10 minutes after initiation. Platelet aggregation inhibition is reversible following cessation of the infusion.

Distribution

Vdss: 22 to 42 L

Metabolism

Negligible

Excretion

Urine (65%) and feces (25%) primarily as unchanged drug

Onset of Action

>90% inhibition of platelet aggregation (reversible after discontinuation) seen within 10 minutes

Half-Life Elimination

2 hours; Note: In ~90% of patients, ex vivo platelet aggregation returns to near baseline in 4 to 8 hours after discontinuation.

Protein Binding

65% (concentration dependent)

Special Populations: Renal Function Impairment

Plasma clearance is decreased by ~40% in patients with CrCl <60 mL/minute and more than 50% in patients with CrCl <30 mL/minute (including those requiring hemodialysis).

To support PCI (administered at the time of elective PCI) for stable ischemic heart disease (high risk features)

Data from a small, single-center, double-blind, placebo-controlled, randomized trial enrolling 202 patients with clinical or angiographic high-risk features (29% with stable angina) undergoing elective or urgent PCI supports the use of high-bolus dose tirofiban in the management of patients with stable ischemic heart disease and high risk features undergoing PCI [Valgimigli 2004]. Additional trials may be necessary to further define the role of tirofiban in this setting.

Contraindications

Severe hypersensitivity reaction (ie, anaphylactic reaction) to tirofiban or any component of the formulation; history of thrombocytopenia following prior exposure to tirofiban; active internal bleeding or a history of bleeding diathesis, major surgical procedure, or severe physical trauma within the previous month

Canadian labeling: Additional contraindications (not in US labeling): History of thrombocytopenia following prior exposure to any other GPIIb/IIIa inhibitor; recent (within the previous 30 days) internal bleeding; history of intracranial hemorrhage or neoplasm, arteriovenous malformation, or aneurysm; history, symptom or findings suggestive of aortic dissection; known coagulopathy, platelet disorder or history of thrombocytopenia; stroke within 30 days prior to hospitalization or any history of hemorrhagic stroke; major surgical procedure or relevant trauma within the previous 6 weeks; malignant or severe uncontrolled hypertension (>180 mmHg/110 mmHg); current use with other GP IIb/IIIa inhibitors; acute pericarditis; cirrhosis or clinically significant liver disease; angina precipitated by obvious provoking factors (eg, arrhythmia, severe anemia, hyperthyroidism, hypotension); recent epidural procedure.

Percutaneous coronary intervention (PCI): IV: Loading dose: 25 mcg/kg administered over 5 minutes or less at the time of PCI; Maintenance infusion: 0.15 mcg/kg/minute continued for up to 18 hours (ACCF/AHA/SCAI [Levine 2011]; Valgimigli 2004)

Stable ischemic heart disease (high-risk features) undergoing elective PCI (off-label use): Loading dose: 25 mcg/kg administered over 5 minutes or less at the time of PCI; Maintenance infusion: 0.15 mcg/kg/minute; was continued for up to 48 hours in the clinical trial (ACCF/AHA/SCAI [Levine 2011]; Valgimigli 2004). Note: Reserve for patients who were not pretreated with clopidogrel or who are undergoing elective PCI with stent implantation with adequate clopidogrel pretreatment (ACCF/AHA/SCAI [Levine 2011]).

Reconstitution

Do not dilute. Determine the volume needed to administer the loading dose using the 15 mL (concentration: 250 mcg/mL) premixed bolus vial or the 100 mL (concentration: 50 mcg/mL) premixed vial or premixed bags. Determine the infusion rate of the maintenance infusion using the 100 mL (concentration: 50 mcg/mL) premixed vial or bags. Do not use bags in series connections.

Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Monitor therapy

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Monitor therapy

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy

Dabigatran Etexilate: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Monitor therapy

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy

Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Monitor therapy

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Ibritumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Tositumomab and Iodine I 131 Tositumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Monitor therapy

Adverse Reactions

Bleeding is the major drug-related adverse effect. Patients received background treatment with aspirin and heparin. Adverse reactions reported are derived from both the high-dose bolus regimen and the dosing regimen used in studies that established the effectiveness of tirofiban. Frequency not always defined.

<1% (Limited to important or life-threatening): Anaphylaxis, hemopericardium, hypersensitivity

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding: The most common complication is bleeding, including retroperitoneal, pulmonary, and spontaneous GI and/or GU bleeding; watch closely for bleeding, especially the arterial access site for the cardiac catheterization. Fatal bleeding has been reported. Use with extreme caution in patients with platelet counts <150,000/mm3, patients with hemorrhagic retinopathy, previous history of GI disease, recent thrombolytic therapy and in chronic dialysis patients. Use caution with administration of other drugs affecting hemostasis. Minimize other procedures including arterial and venous punctures, IM injections, nasogastric tubes, etc.

• Thrombocytopenia: Profound thrombocytopenia has been reported with use of tirofiban. If during therapy platelet count decreases to <90,000/mm3, monitor platelet counts to exclude pseudothrombocytopenia. If thrombocytopenia is confirmed, discontinue tirofiban and heparin if administered concurrently. Platelet counts should recover rapidly (within 1 to 5 days) after discontinuation. Previous exposure to a glycoprotein IIb/IIIa inhibitor may increase the risk of thrombocytopenia. Use is contraindicated in patients with a history of thrombocytopenia following exposure to tirofiban. Specific management guidelines for GP IIb/IIIa induced thrombocytopenia have been published (Huxtable 2006; Llevadot 2000).

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Information related to use in pregnancy is limited; successful use during pregnancy has been described in a case report (Boztosun, 2008).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.